Apparatus and method for blocking activation of tissue or conduction of action potentials while other tissue is being therapeutically activated

ABSTRACT

A desired effect is produced by therapeutically activating tissue at a first site within a patient&#39;s body and a corresponding undesired side effect is reduced by blocking activation of tissue or conduction of action potentials at a second site within the patient&#39;s body by applying high frequency stimulation and/or direct current pulses at or near the second site. Time-varying DC pulses may be used before or after a high frequency blocking signal. The high frequency stimulation may begin before and continue during the therapeutic activation. The high frequency stimulation may begin with a relatively low amplitude, and the amplitude may be gradually increased. The desired effect may be promotion of micturition or defecation and the undesired side effect may be sphincter contraction. The desired effect may be defibrillation of the patient&#39;s atria or defibrillation of the patient&#39;s ventricles, and the undesired side effect may be pain.

RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.09/859,280, filed May 17, 2001, which is hereby incorporated herein inits entirety.

FIELD

This invention relates to techniques for blocking activation ofelectrically excitable tissue within a patient's body, and moreparticularly relates to techniques for producing a desired effect bytherapeutically activating tissue at a first predetermined site within apatient's body and for reducing a corresponding undesired side effect byblocking activation of tissue at a second predetermined site within thepatient's body.

BACKGROUND

It is often desirable to therapeutically activate excitable tissue, suchas nerve, muscle, or glandular cells of a patient by electricalstimulation or via medications. An undesirable side effect of suchtherapeutic activation of excitable tissue is that other tissue, eithernearby or distant, may be undesirably activated, either directly by thesame mode of activation, or indirectly by sensory feedback or otherreflexes.

Generally, undesired action potentials in sensory nerves or dorsal rootsmay either be disagreeable to the patient or cause contrary effects.When stimulating to assist peristalsis in the esophagus, ureter,stomach, or intestine, co-contraction of sphincters or disagreeablesensations or reverse peristalsis might be undesirable. For instance, ifa patient is unable to control urination or defecation, stimulation ofperipheral nerves or ventral roots to contract a patient's bladder formicturition or to move bowel contents may be desirable. Such activation,or even lower amplitude stimulation, however, will typically createaction potentials in sphincters, such as those in the external urethraor anus. Such action potentials will tend to cause the sphincters tocontract, which may result in an inability to pass urine or fecal matterbeyond the sphincters. In addition, increased pressure in the bladdercaused by simultaneous compression of the patient's bladder andcontraction of the patient's external urethral sphincter may lead toinjury to the patient, including increased pressure and damage to eitheror both the bladder and the kidneys. A conventional approach that hasbeen proposed for patients that are substantially paralyzed is to cutthe patient's nerves that lead back into the spinal cord (dorsal roots)so that the stimulation of the bladder does not cause a lot of neuralactivity in the spinal cord. If a patient's bladder is significantlyoverfilled, autonomic dysreflexia may occur causing a very large anddangerous increase in the patient's blood pressure, which may cause astroke.

When stimulating to defibrillate a patient's heart, extremely intensepain is typically inflicted upon the patient due to simultaneousactivation of many afferent fibers, some of which may even be the axonsof nociceptors.

When stimulating certain motorneurons, activations directly or by spinalreflex of antagonistic motorneurons and muscles may interfere with thedesired motion, necessitating an increase in the strength ofstimulation, which causes increased rigidity of a patient's joints.

Electrical excitation of tissue at low frequencies (e.g., less than 100Hertz) has been known to cause action potentials in nerve and muscle. Inaddition, some techniques have been described to block action potentialsin certain nerve fibers, with the best observations done in animalexperiments.

Tanner (Nature, vol. 195, 1962: 712-713) and Woo & Campbell (Bull. L. A.Neurol. Soc., vol. 29, 1964:87-94) showed that 20,000 Hz stimulation ofa nerve is able to block passing action potentials, with larger voltages(amplitudes) needed to progressively block smaller fibers. Recently,from therapeutic stimulation of the brain in patients with tremor andother symptoms of Parkinson's disease, evidence has mounted that highfrequency stimulation (100-185 Hertz) keeps neurons depolarized, andhence incapable of producing action potentials (Benabid et al., Lancet,vol. 337, 1991: 403-406; Benazzouz et al., Neurosci. Lett., vol. 189,1995: 77-80). High frequency stimulation of the spinal cord or nerves(250 Hertz and more) has been anecdotally reported to relieve chronicpain, but whether this works by blocking of action potentials is unknown(Picaza et al., Surg. Neurol., vol. 4, 1975: 105-114 and 115-126;Sheldon et al., Surg. Neurol., vol. 4, 1975: 127-132; Bennett et al.,Neuromodulation, vol. 2, 1999: 202-210).

Mendel & Wall (J. Physiol., vol. 172, 1964: 274-294) and Campbell & Woo(Bull. Los Angeles Neurol. Soc., vol. 31, 1966: 63-71) demonstrated asimilar amplitude-dependent blocking of action potentials inprogressively smaller axons using direct current (D.C.) signals.Recently, evidence has developed that repetitive stimulation in rats ofthe brain area called the amygdala, which can cause seizures due tokindling, can have its kindling effects quenched by use of 5 to 15microampere D.C. currents applied once a day for 15 minutes (Weiss etal., Exper. Neurol., vol. 154, 1998: 185-192).

The disadvantage of direct current pulses is that they can lead totissue or electrode damage (Pudenz, et al, Surg. Neurol., vol. 4,1975:265-270) or to asynchronous repetitive action potential discharges(Manfredi, Arch. Ital. Biol., vol 108, 1970: 52-71; Sassen & Zimmerman,Pflugers Arch. Gesamte Physiol. Menschen Tiere, vol. 341, 1973:179-195).

Van den Honert & Mortimer (IEEE trans. BME., vol. 28, 1981: 373-378 and379-382) developed a technique to create action potentials thatpropagate in only one direction along axons using a tripolar cuff withthree electrodes and two regulated current stimulators. This method wasused by Brindley & Craggs (J. Neurol. Neurosurg. Psychiat., vol. 43,1980: 1083-1090) to excite only the smaller (parasympathetic) fibers inspinal nerve roots and peripheral nerves for bladder emptying. Ungar,Mortimer & Sweeney (Ann. Biomed. Engng, vol. 14, 1986: 437-450) werealso able to generate unidirectionally propagating action potentials innerves using an asymmetric monopolar electrode cuff. However, both ofthese partial-blocking techniques require complete encirclement of theaxons of interest with non-conducting materials, something which thehigh frequency and D.C. techniques do not require.

In order to minimize undesirable side effects associated withtherapeutic activation of tissue, including, but not limited to, theside effects mentioned above, it may be desirable to deactivate orinhibit certain excitable tissue during the time that the desired effectis being produced in the therapeutically activated tissue.

It would, therefore, be desirable to block action potentials in tissuethat are deliberately generated from low frequency stimulation. Theblock may not be complete, and there may be asynchronous, evenrepetitive generation of some action potentials in the process, butunder certain circumstances, it may be possible to prevent most of theaction potentials in certain nerves that otherwise may be caused byother electrodes in nearby tissue that use deliberate low frequencypulses to cause action potentials. The volume of tissue recruited nearthe deliberate “activation” electrodes and the volume of tissueinhibited near the “blocking” electrodes would both depend upon theparameters of stimulation, especially the amplitude and pulse width.

SUMMARY OF EXEMPLARY EMBODIMENTS

In accordance with certain inventive principles, a desired effect isproduced by therapeutically activating tissue at a first site within apatient's body and a corresponding undesired side effect is reduced byblocking activation of tissue at a second site within the patient's bodyby applying high frequency stimulation and/or one or more direct currentpulses at or near the second site.

In accordance with various inventive principles, the desired effect maybe promotion of micturition; the undesired side effect may be sphinctercontraction; the first site may be the patient's bladder dome, sacralroots, or pelvic plexus; and the second site may be the patient's:sacral dorsal roots, spinal dorsal columns, conus medullaris, pudendalnerve, hypogastric plexi, or perineal nerve.

The desired effect may be promotion of defecation; the undesired sideeffect may be sphincter contraction, elevated pelvic floor, or sharpano-rectal angle; the first site may be the patient's: hypogastricplexus, pelvic plexus, nerves to rectum, sacral roots, pelvic plexus, orrectal muscle; and the second site may be the patient's: sacral dorsalroots, spinal dorsal columns, conus medullaris, pudendal nerve, ornerves to the patient's pelvic floor muscles.

The desired effect may be peristalsis of the patient's esophagus; theundesired side effect may be contraction at the patient'sgastroesphageal sphincter; the first site may be the patient's:esophagus, nerves to the patient's esophagus, pharynx, or nerves to thepatient's pharynx; and the second site may be the patient's: hiatalesophagus area near the patient's diaphragm, or nerves to the patient'sesophagus.

The desired effect may be peristalsis of the patient's ureter; theundesired side effect may be closure of the patient's anti-reflux valvesnear the patient's bladder trigone; the first site may be the patient's:renal pelvis or a portion of the patient's ureter; and the second sitemay be the patient's: base of the bladder near an entrance of a ureter,hypogastric plexus, or pelvic plexus.

The desired effect may be peristalsis of the patient's stomach; theundesired effect may be closure of the patient's pyloric sphincter; thefirst site may be the patient's: stomach wall muscles or the nervesleading to the patient's stomach wall muscles; and the second site maybe the patient's: muscle fibers of the pyloric sphincter or nerves tothe pyloric sphincter.

The desired effect may be peristalsis of the patient's intestine; theundesired effect may be closure of the patient's ileocecal valve to thepatient's colon; the first site may be the patient's: intestinal wallsmooth muscle, hypogastric plexus, or nerves to the patient'shypogastric plexus; and the second site may be the patient's: ileocecalvalve, mesenteric ganglia, dorsal root, spinal dorsal columns, orsplanchnic nerves.

The desired effect may be selected from the group consisting of:defibrillation of the patient's atria or defibrillation of the patient'sventricles; the undesired side effect may be pain; the first site may benear a heart pacing/defibrillation lead: inside the patient's heartchambers or outside the patient's heart chambers; the second site may bethe patient's: vagus nerve, branches of the patient's vagus nerve fromthe patient's heart, thoracic sympathetic nerves, ansa subclavia,sympathetic trunk ganglia (T1-T4), stellate ganglia, cervical ganglia(C1-C8), celiac plexus, brachial plexi, dorsal roots (C1-T4), spinaldorsal columns, or dorsal roots.

The desired effect may be extension of the patient's leg; the undesiredside effect may be co-contraction of the antagonist muscles; the firstsite may be the patient's femoral nerve to the patient's quadricepsfemoris; and the second site may be the patient's tibial nerve to thepatient's gastrocnemius muscle.

The desired effect may be movement of one of the patient's joints in apredetermined direction; the undesired side effect may be co-contractionof antagonist muscles; the first site may be the patient's peripheralnerve; and the second site may be the patient's nerve branch to anantagonist muscle.

The high frequency blocking stimulation may begin before and continueduring the therapeutic activation. The high frequency blockingstimulation may begin with a relatively low amplitude, and the amplitudemay be gradually increased. The high frequency blocking stimulation maybe terminated by gradually reducing the amplitude of the high frequencystimulation.

A sensor may be included for sensing a state of the tissue at the secondsite or at a more remote site. Means, responsive to the sensor, foradjusting the pulse amplitude, pulse width, pulse frequency, pulse dutycycle, pulse polarity, or pulse waveform of the high frequency blockingstimulation at the second site may also be included.

Direct current pulses may be used to block activation of the tissue atthe second site. If ramped up or down gradually, this may allow neuronalaccommodation and prevent action potentials. Direct current pulses mayalso be used before or after a series of high frequency blockingsignals, so that much of the stimulation for blocking has charge balanceto protect the electrodes or tissue.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a diagrammatic illustration of a system for blockingactivation of tissue within a patient according to various inventiveprinciples.

FIG. 2 shows blocking stimulation starting before and ending afterintended effect stimulation.

FIGS. 3 a-3 d show various combinations and permutations of highfrequency and/or direct current blocking pulses with and/or withoutramping at the beginning and/or end of the pulses.

FIG. 4 is a flow chart depicting steps that may be performed to blockactivation of tissue in accordance with certain inventive principles.

FIG. 5 is a schematic diagram showing electrode placement for promotionof micturition in accordance with various inventive principles.

FIG. 6 is a schematic diagram showing electrode placement in a patient'sintrathecal space near the patient's dorsal root for blocking sensationsassociated with stimulation of another part of the patient's body.

FIG. 7 is a schematic diagram showing electrode placement for assistingperistalsis of a patient's esophagus and/or emptying the patient'sstomach.

FIG. 8 is a schematic diagram showing electrode placement for extendinga patient's lower leg.

FIG. 9 is a schematic diagram showing electrode placement for promotionof defecation in accordance with various inventive principles.

FIG. 10 is a schematic diagram showing suitable electrode placement forreducing pain perceived by a patient associated with defibrillationpulses.

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

Evidence, from stimulation of the brain for tremor and other symptoms ofParkinson's disease, indicates that high frequency stimulation keepsneurons depolarized, and hence incapable of causing an action potential.See A. L. Benabid et al., Long-Term Suppression of Tremor by ChronicStimulation of the Ventral Intermediate Thalamic Nucleus, the Lancet,vol. 337, 1991, pp. 403-406. Accordingly, the therapies of deep brainstimulation to block tremor and to block neuronal pathways that preventdesired volitional movements (freezing, akinesia, bradykinesia) oftenuse high frequency stimulation. For instance, commonly assigned U.S.Pat. Nos. 5,716,377 and 5,833,709 disclose such systems and methods andare incorporated herein by reference. As used herein, the phrase “highfrequency stimulation” refers to electrical stimulation of at leastapproximately 100-120 Hz, while “low frequency stimulation” refers toelectrical stimulation of less than approximately 100 Hz.

FIG. 1 is a schematic view of a patient 110 having an implant of aneurological stimulation system employing a preferred form of thepresent invention. A system in accordance with the principles of theinvention may employ an implantable pulse generator 114 to producestimulation pulses to various predetermined sites within a patient'sbody. For instance, as depicted in FIG. 1, the concept of applying highfrequency blocking stimulation with electrode 140 is depictedschematically. High frequency stimulation is applied in order to preventan undesirable side effect of spinal cord stimulation applied viaelectrode 118. In accordance with the principles of this invention, thesite at which an undesirable side effect is blocked using high frequencystimulation will often be located in close proximity to the locationwithin the patient's body at which low frequency intended effectstimulation is applied. Nevertheless, the two types of stimulation maybe applied in areas of a patient's body that are relatively far apart,as shown, for instance, in FIG. 1. Another example is applying highfrequency blocking stimulation to block pain perceived by a patientwhile administering a defibrillation pulse to the patient's heart, theblocking stimulation may be applied in locations away from the heart, asdescribed in more detail below.

In a preferred embodiment, implantable signal generator 114 may be amodified signal generator, such as Model 7424 manufactured by Medtronic,Inc. under the trademark Itrel7, or pulse generator 114 might not have abattery and might instead get programming signals and energy from amodified exterior transmitter 120 and antenna 124 like a radio frequencysystem manufactured by Medtronic, Inc. known as X-trel7 or Mattrix7.Signal generator 114 could simultaneously produce both high and lowfrequency stimulation, for instance, at frequencies above and below 100Hz, respectively. Alternatively, signal generator 114 could outputeither high or low frequency stimulation and a second signal generator,not shown, could be used to output the other type of stimulation.

For spinal cord stimulation (SCS), signal generator 114 is commonlyimplanted subcutaneously in a human body in the abdomen or back. Inaccordance with the principles of this invention, one or more signalgenerators may be placed near a location that will be therapeuticallyactivated or near an area in which activation will blocked or near bothsuch types of areas. Electrodes 140 and 118 may be operatively coupledto signal generator 114 by leads 115 and 116, respectively.Alternatively, Electrodes 140 and 118 may be operatively coupled tosignal generator 114 by a single lead.

FIG. 2 depicts high frequency blocking stimulation beginning earlier intime than the intended effect stimulation and continuing until after theintended effect stimulation has finished. By starting the high frequencyblocking stimulation before and continuing it after the intended effectstimulation is applied, undesirable side effects associated with theintended effect stimulation may be blocked more effectively than wouldbe possible if the high frequency blocking stimulation did not startuntil the same time as, or after, and/or stopped at the same time, orbefore, the intended effect stimulation. The intended effect stimulationmay be a single pulse or multiple pulses.

The waveform at the top of FIG. 3 a depicts high frequency blockingstimulation pulses that start and stop without any ramping or gradualincrease or decrease of the amplitude of the pulses. The middle andlower waveforms, depict blocking pulse waveforms in which the amplitudeof the waveform is ramped up or gradually increased at the beginning ofthe waveform, and ramped down or gradually decreased at the end of thewaveform, respectively. Such ramping may be used in order to minimizecreation of any action potentials that may be caused by more abruptlystarting and/or more abruptly stopping the high frequency blockingstimulation.

Creation of a blocking signal without action potentials being caused bythe high frequency blocking pulses is desirable. As shown in FIG. 3 b, astraight direct current pulse may be employed throughout the time forblocking. It may be depolarizing, especially if it has a gradual rampthat allows accommodation of the neural tissue to prevent actionpotentials from developing. Action potentials that approach the regionrun into areas where neuronal sodium gates are already affected and thuscannot open. It may also be of opposite sign, hyperpolarizing. Thisprevents action potentials from starting when the transmembranepotential cannot be sufficiently reduced to open the sodium channels,but action potentials approaching the region might still pass through.

A danger associated with direct current pulses is that there may beelectrode dissolution and neuronal damage due to a steady and longdistance flow of ions. However, such stimulation may be appliedrelatively infrequently, for instance just a few times per hour or permonth, depending on the application. The ability to shield the sideeffects, therefore, may outweigh the dangers from intermittent directcurrent stimulation.

FIG. 3 c shows a combination of modes for blocking. There is a gradualDC ramp and then a series of high frequency pulses. The ramp may produceaccommodation of neurons, and prevent any action potentials. Thecontinuation of high frequency stimulation may keep neurons deactivated,while still producing charge-balanced pulses. This technique may be usedto advantage to prevent initial action potentials and to minimizeelectrode or tissue problems.

FIG. 3 d shows multiple combinations with a variety of DC pulses. Theinitial pulse might have an exponential rise instead of a linear rise.The end of the blocking signal might also use a DC pulse to allow theneuronal tissue to return to its excitable state without causingactivations, for example, anodal break.

FIG. 4 is a flow chart depicting steps that may be performed to blockactivation of tissue in accordance with certain inventive principles. Atstep 402, high frequency blocking stimulation is started and mayoptionally be ramped as described above with reference to FIG. 3. Atstep 404, low frequency intended effect stimulation is started. At step406, a determination may be made as to how effectively the highfrequency stimulation is blocking one or more undesirable side effectsassociated with the intended effect stimulation. This determination maybe performed by a suitable sensor for measuring various parameters, suchas movement of limb, contraction of sphincter, or any other suitablemeasurement indicating the degree to which an undesired side effect hasbeen blocked.

If the blocking stimulation is determined to be insufficient, adetermination is made as to whether a predetermined limit on the amountof blocking stimulation to be applied has been reached, as shown at 408and 410. If the blocking stimulation limitation has not yet beenreached, the blocking stimulation may be increased at step 402, the lowfrequency stimulation may be continued as shown in step 404, and thedeterminations may be made again as shown at 408 and 410.

If the blocking stimulation is determined to be sufficient, the intendedeffect, also referred to as target tissue, stimulation may be continuedfor as long as is desirable, as shown at 408 and 412. After terminatingthe intended effect stimulation at 412, the high frequency blockingstimulation may be terminated, as shown at 414.

Turning now to example applications of the principles of this invention,FIG. 5 is a schematic diagram showing electrode placement for promotionof micturition in accordance with various inventive principles. Anteriorsacral root 513 is shown originating from spinal cord 512, which isshown in a sectional view. Electrode 515 is shown in close proximity toanterior sacral root (S1-S4) 513. Low frequency intended effectstimulation may be applied to sacral root 513 via electrode 515 in orderto promote micturition by causing action potentials in nerve 507 leadingto bladder 510. In order to block activation of external sphincter 508of the urethra in the pelvic floor muscles of a patient, high frequencyblocking stimulation may be applied near branch 509 of pudendal nerveleading to external sphincter 508. The high frequency blockingstimulation is preferably started before and continued after theapplication of the low frequency intended effect stimulation. Inaddition to the sacral roots, low frequency intended effect stimulationmay also be applied to other parts of the patient's body, including, butnot limited to, the patient's bladder dome and/or the patient's pelvicplexis of nerves. Sphincter contraction may also be prevented byapplication of high frequency blocking stimulation at locations otherthan the patient's pudendal nerve, including, but not limited to, thepatient's sacral dorsal roots, spinal dorsal columns, conus medullaris,hypogastric plexus, and perineal nerve.

FIG. 6 is a schematic diagram showing placement of electrode 614 in apatient's intrathecal space near the patient's dorsal root for blockingsensations associated with stimulation of another part of the patient'sbody. As discussed in the Background of the Invention section above,stimulating nerves leading to bladder 510, without blocking activationof the external sphincter 508, may lead to reflex sympathetic dystrophyand stroke, among other complications. Rather than cut the afferentnerves, as has been proposed in U.S. patents to Tanagho and Schmidt etal. U.S. Pat. Nos. 4,607,639; 4,703,755; and 4,771,779)*, the dorsalroots may be stimulated at high frequency to block their activationwhile the bladder is contracting, thereby reversibly blocking activationof the dorsal root tissue, as shown in FIG. 6. In addition to preventingreflex sympathetic dystrophy, application of high frequency stimulationvia lead 616 may prevent undesirable sensation associated with the lowfrequency stimulation applied to contract the patient's bladder bypreventing activation of the patient's dorsal root. As will be apparent,undesirable sensations from many sources other than the patient'sbladder may also be blocked in a similar manner. As will also beapparent, electrode 614 may also be placed in other suitable areas inorder to block activation of other tissue thereby preventing otherundesirable effects of low frequency intended effect stimulation appliedelsewhere in a patient's body. For instance, electrode 614 may be placedoutside the arachnoid membrane 660 in the subdural space 654 or outsidedura 652 in the epidural space 670.

Blocking signals can be delivered at any of these sites to not onlyprevent pain, but also prevent nerve action potentials from entering thespinal cord and causing undesired reflexes. If pain is the chiefundesired side effect from nerve or tissue activation, then it ispossible to block it as it ascends the spinal cord near the surface ofthe ventrolateral quadrant, in the spinothalamic tract, on the oppositeside of the spinal cord, since pain fibers cross near their point oforigin. It may be advantageous to place an electrode under the dura,next to the pial surface in this case, to not also cause loss ofsensations or motor control on that opposite side.

FIG. 7 is a schematic diagram showing electrode placement for assistingperistalsis of a patient's esophagus and/or emptying the patient'sstomach. Branches of vagus nerve 46 are shown along esophagus 38 andstomach 35 and connecting to myenteric nervous system 44, which arelocal neurons involved in peristaltic contraction of the esophagus. Highfrequency blocking stimulation may be applied via electrode 32 near thehiatal portion of the esophagus, which is where the bottom portion ofthe esophagus 38 meets upper portion of stomach 35. Low frequencyintended effect stimulation may then be applied by upper electrode 31 topromote peristalsis of the esophagus in order to move food down theesophagus and into the stomach. The high frequency blocking stimulationwill prevent the low frequency intended effect stimulation fromundesirably causing the hiatal portion of the esophagus to contract.Peristalsis of the patient's esophagus may also be promoted byapplication of low frequency intended effect stimulation of thepatient's pharynx. Contraction of the patient's gastroesphagealsphincter may be prevented by application of high frequency blockingstimulation to nerves leading to that portion of the patient'sesophagus.

In a similar manner, contraction of pyloric sphincter 37 may beprevented by applying high frequency stimulation via electrode 39 whileapplying low frequency stimulation to the stomach muscle 35 or toelectrodes 33 and 34 located in close proximity to descending branchesof celiac ganglia 40 in order to move food from the patient's stomach 35to the patient's intestine 36.

Peristalsis of the ureter, to move urine to the bladder, and theintestine, to move food materials along, are also normal physiologicalfunctions of the urinary and digestion system that may becomecompromised by trauma or disease. Although not depicted in FIG. 7, inthese cases, there could be activation at low frequency to start theperistalsis of material. In the case of the ureter, the activationshould be in the renal pelvis portion of the kidney, or near the top ofthe ureter, above any segment that is paralyzed, or at intact nervesgoing to those structures. In the case of the intestine, activationshould be anywhere along the intestine that there is a functionalproblem, or at intact nerves going to that portion of bowel. Activationmay have to be done in a delayed, sequential process along the length ofthe structure as well, to keep the peristalsis moving adequately.Blocking of excitation using high frequency stimulation and/or directcurrent potentials should be done where a particular valve may not befunctionally opening as required. In the case of the ureter, this mightbe near the bladder's trigone, where an anti-reflux valve usually helpsprevent urine flow back toward the kidney, or at intact nerves thatinnervate that portion of the bladder. In the case of the intestine,this might be at the ileocecal valve, or at nerves that go to that areaof the intestine. In cases where peristalsis can be restored by lowfrequency activation and there is undesirable sensation being produced,blocking can be done on the dorsal columns or dorsal roots of sensorysignals going to the spinal cord and brain. It is conceivable thatblocking of tissue excitation should be done in two locations: at anonfunctioning valve, to prevent excitation by the peristaltic wave,done at an appropriate time related to the speed of peristalsis anddistances, and at the spinal sensory pathways, to prevent passage ofaction potentials, mostly useful near the time the desired peristalsisis begun by low frequency activation.

Referring to FIG. 8, electrode placement is depicted for functionalelectrical stimulation to control muscles for extending a patient's leg.Nerve 54, leading to muscle 50, may be stimulated by electrode 56causing muscle 50 to contract such that the patient's tibia 52 will movein the direction of arrow 58, thereby straightening the patient's leg.Such stimulation may undesirably cause simultaneous contraction of anantagonist muscle, such as muscle 51. Therefore, nerve 55 may bestimulated with high frequency blocking stimulation at electrode 57 toprevent action potentials in nerve 55 from causing contraction of muscle51. As will be apparent, applying varying levels of high frequencystimulation to muscle 51 may be desirable in order to move tibia 52 in acontrolled fashion. The amount and/or duration of either or both typesof stimulation may be controlled as described above in connection withFIG. 4. For example, when a person is standing up, tension in bothmuscles is desirable. Low frequency stimulation from electrode 56 may beapplied to both nerves 54 and 55, while high frequency stimulation maybe applied to modulate the action potentials that can get through tomuscle 51, thereby reducing the amount of axons in nerve 55 that causecontraction of muscle 51.

FIG. 9 is a schematic diagram showing electrode placement for promotionof defecation in accordance with various inventive principles. Nerves 75outside descending colon 70 and nerve plexus 76 in the wall of rectum 71are shown. Low frequency stimulation in the area of pelvic plexus nervesto rectum 77, which could be used to contract the rectum to promotedefecation, may also stimulate pudendal nerve 78, directly, or by reflexarc, in a similar manner as described above with respect to the bladderand FIG. 5. Accordingly, high frequency blocking stimulation may beapplied via electrode 79 to pudendal nerve 78 to prevent actionpotentials in pudendal nerve 78, which would undesirably cause pelvicfloor muscles or anal sphincter muscles 72 to contract. Pelvic plexusnerves 77 originate from the sacral roots as does the pudendal nerve 78.Using low frequency sacral root stimulation, pudendal nerve 78 will beactivated at a lower amplitude than pelvic plexus nerves 77 becausepudendal nerve 78 contains larger diameter axons. At higher amplitudesof low frequency stimulation the rectum may contract, but the pudendalnerve 78 will be activated and will prevent defecation. This phenomenonalso applies to stimulation of the nerves discussed with respect to thebladder. Accordingly, the bladder and the rectum cannot be contractedwith low frequency stimulation until its sphincter has already beenundesirably contracted, absent high frequency blocking stimulationapplied to a nerve leading to the sphincter. To promote defecation, lowfrequency intended effect stimulation may also be applied at other areasin a patient's body, including, but not limited to, the patient'shypogastric plexus, pelvic plexus, nerves along the patient's rectum,and sacral roots. Undesired side effects of such low frequency intendedeffect stimulation, may include, but are not limited to, sphinctercontraction, elevation of the pelvic floor, and promotion of a sharpano-rectal angle. These can be prevented by application of highfrequency or direct current blocking stimulation to other part or thepatient's body, including, but not limited to, the patient's sacraldorsal roots, spinal dorsal columns, conus medullaris, and nerves to thepatient's pelvic floor muscles.

As mentioned above, defibrillation of a patient's heart by use of strongelectric pulses is extremely painful. Commonly assigned U.S. Pat. No.5,817,131, which issued to Elsberry et al. and is incorporated herein byreference, discloses blocking of pain messages using spinal cordstimulation or stimulation in other sites in peripheral or centralpathways. The Elsberry '131 patent discloses blocking of pain messagesvia the Gate Control Hypothesis, which involves stimulation typically ata frequency below 100 Hz near the doral columns. Presumably, largerdiameter fibers are stimulated to block the smaller diameter fibers,which carry pain and temperature. In accordance with the principles ofthe instant invention, high frequency stimulation, in other words,stimulation at frequencies above 100 Hz, may be used to blocksubstantially all afferent nerves near the heart, including the smalldiameter fibers which often carry pain messages. High frequency ordirect current blocking stimulation may preferably be applied toperipheral nerves, including nerves from the heart, such as vagus orsympathetic nerves or both, which tend to have small diameter axons.

FIG. 10 is a schematic diagram showing suitable electrode placement forreducing pain perceived by a patient associated with defibrillationpulses. Pain information may travel from the heart by going to the leftin FIG. 10 through the parasympathetic vagus nerve 81 due to itsbranches, 82-84. Pain information may also travel from the heart to theright in FIG. 10 into the sympathetic system via nerves exiting theheart 91. These nerves bring information, especially about pain, to thestellate sympathetic ganglia 85 or to the T1-T4 thoracic ganglia 86, 88,89, and 90. In order to block pain signals in sympathetic efferentnerves 91, electrodes could be placed near those nerves either before,93 and 100, or after, 94 and 99, they pass to the sympathetic ganglia85, 86, 88, 89, and 90. These electrodes may be placed endoscopicallyusing a needle near the branches of these nerves. While defibrillating apatient's atria or ventricles, low frequency intended effect stimulationmay be applied via a heart pacing/defibrillation lead inside thepatient's heart chambers or via a heart pacing/defibrillation leadoutside the patient's heart chambers. Pain associated withdefibrillating a patient's atria or ventricles may be prevented byapplication of high frequency or direct current blocking stimulation tolocations within the patient's body including, but not limited to, thebilateral vagus nerves, branches of the patient's vagus nerves near thepatient's heart, sympathetic nerves near the heart, ansa subclavia,sympathetic trunk ganglia (T1-T4), stellate ganglia, cervical ganglia,celiac plexus, brachial plexi, dorsal columns and dorsal roots (C1-T4).

If the ventricles are being defibrillated, blocking stimulation may beapplied to lower ganglia 89 and 90 via electrode 93, for example. Atrialdefibrillation, on the other hand, will typically be needed more often,for instance many times per day. High frequency stimulation may beapplied to electrodes 94, 99 or 100 for the upper sympathetic ganglia85, 86, 88 and electrode 96, 97 or 98 may be used for blocking paininformation transmitted via the vagus nerve, depending upon wheredefibrillation occurs.

The preferred embodiments may be altered or amended without departingfrom the true spirit and scope of the invention, as defined in theaccompanying claims.

1. Apparatus for producing a desired effect by activating tissue at afirst predetermined site within a body and for reducing a correspondingundesired side effect by blocking activation of tissue or conduction ofaction potentials at a second predetermined site within the body, theapparatus comprising: first generator means for producing low frequencystimulation; second generator means for producing high frequency and/ordirect current pulse stimulation; and a first electrode operativelycoupled to the first generator means, the first electrode being adaptedto activate tissue at the first predetermined site by applying lowfrequency stimulation; and a second electrode coupled to the secondgenerator means, the second electrode being adapted to block activationof electrically excitable tissue at the second site by applying highfrequency stimulation or one or more direct current pulses, or both highfrequency stimulation and one or more direct current pulses, at or nearthe second site such that the high frequency stimulation and/or thedirect current pulses prevent the low frequency stimulation applied atthe first site from activating the electrically excitable tissue, orcausing conduction of action potentials, at the second site.
 2. Theapparatus of claim 1 wherein: the first generator means comprises afirst signal generator for producing low frequency stimulation; and thesecond generator means comprises a second signal generator for producinghigh frequency and/or direct current pulse stimulation.
 3. The apparatusof claim 2 further including at least one implantable lead operativelycoupling the first and second electrode with the first and second signalgenerators.
 4. The apparatus of claim 2 further including a firstimplantable lead operatively coupling the first electrode with the firstsignal generator, and a second implantable lead operatively coupling thesecond electrode with the second signal generator.
 5. The apparatus ofclaim 1 wherein the first generator means and the second generator meanscomprise at least one signal generator capable of simultaneouslyproducing both low frequency stimulation and high frequency stimulationor direct current pulses.
 6. The apparatus of claim 5 further includingat least one implantable lead operatively coupling the first and secondelectrode with the signal generator.
 7. The apparatus of claim 5 furtherincluding a first implantable lead operatively coupling the firstelectrode with the signal generator, and a second implantable leadoperatively coupling the second electrode with the signal generator. 8.The apparatus of claim 5, wherein the second generator means furtherincludes means for beginning before, and continuing during theactivation, the high frequency stimulation or the direct current pulsesor both the high frequency stimulation and the direct current pulses. 9.The apparatus of claims 8, wherein the second generator means furtherincludes means for beginning the high frequency stimulation or thedirect current pulses or both the high frequency stimulation and thedirect current pulses with a relatively low amplitude and graduallyincreasing the amplitude.
 10. The apparatus of claim 1, wherein thesecond generator means further includes means for beginning before, andcontinuing during the activation, the high frequency stimulation or thedirect current pulses or both the high frequency stimulation and thedirect current pulses.
 11. The apparatus of claim 10, wherein the secondgenerator means further includes means for beginning the high frequencystimulation or the direct current pulses or both the high frequencystimulation and the direct current pulses with a relatively lowamplitude and gradually increasing the amplitude.
 12. The apparatus ofclaim 11, wherein the second generator means further includes means forterminating the high frequency stimulation or the direct current pulsesor both the high frequency stimulation and the direct current pulses bygradually reducing the amplitude of the high frequency stimulation orthe direct current pulses or both the high frequency stimulation and thedirect current pulses.
 13. The apparatus of claim 12, furthercomprising: a sensor for sensing at the second site or at a site that isremote from both the first site and the second site; and means,responsive to the sensor, for adjusting at least one parameter of thehigh frequency stimulation or the direct current pulses or both the highfrequency stimulation and the direct current pulses, the parameter beingselected from the group consisting of: pulse amplitude, pulse width,pulse frequency, pulse duty cycle, pulse polarity, and pulse waveform.14. The apparatus of claim 12, further comprising: a sensor for sensingat the second site or at a site that is remote from both the first siteand the second site; and means, responsive to an indication from thesensor of activation at the second site or at the remote site, forapplying the high frequency stimulation or the direct current pulses orboth the high frequency stimulation and the direct current pulses to thesecond site.
 15. The apparatus of claim 1, wherein the second generatormeans further includes means for terminating the high frequencystimulation or the direct current pulses or both the high frequencystimulation and the direct current pulses by gradually reducing theamplitude of the high frequency stimulation or the direct current pulsesor both the high frequency stimulation and the direct current pulses.16. The apparatus of claim 1, further comprising: a sensor for sensingat the second site or at a site that is remote from both the first siteand the second site; and means, responsive to the sensor, for adjustingat least one parameter of the high frequency stimulation or the directcurrent pulses or both the high frequency stimulation and the directcurrent pulses, the parameter being selected from the group consistingof: pulse amplitude, pulse width, pulse frequency, pulse duty cycle,pulse polarity, and pulse waveform.
 17. The apparatus of claim 1,further comprising: a sensor for sensing at the second site or at a sitethat is remote from both the first site and the second site; and means,responsive to an indication from the sensor of activation at the secondsite or at the remote site, for applying the high frequency stimulationor the direct current pulses or both the high frequency stimulation andthe direct current pulses to the second site.
 18. The apparatus of claim1, further comprising: a sensor for sensing at the second site or at asite that is remote from both the first site and the second site; andmeans, responsive to an indication from the sensor of activation at thesecond site or at the remote site, for applying the high frequencystimulation or the direct current pulses or both the high frequencystimulation and the direct current pulses to the second site.
 19. Theapparatus of claim 1, wherein the first generator means producesstimulation at a frequency less than 100 Hertz, and the second generatormeans produces stimulation at a frequency greater than 100 Hertz. 20.The apparatus of claim 19, wherein the second generator means producesstimulation at a frequency greater than 100 but less than 185 Hertz. 21.The apparatus of claim 20, wherein the second generator means producesstimulation at a frequency of at least 250 Hertz.